Fatal unintentional poisonings from pharmaceutical opioids have increased more than three-fold in the last decade, reaching epidemic proportions. Naloxone is an effective, Food and Drug Administration approved opioid antidote usually administered by first responders in emergency settings to reverse respiratory depression due to opioid poisoning. Community-based harm reduction organizations have developed effective overdose education and naloxone distribution programs for heroin and illicit pharmaceutical opioid users in a number of states. Widespread prescribing of naloxone for take-home use to patients on prescription opioids may prevent overdose deaths through earlier treatment. Primary care settings in large health care systems, offer the opportunity to reach many individuals at risk for opioid overdose, particularly individuals on high dose opioids. In the primary care setting, patients at risk can be identified and can be counseled on overdose risk, improving communication between clinicians and patients about the risks of opioids. Primary care providers can also prescribe naloxone. In this study we will examine the key barriers and facilitators to prescribing naloxone for take-home use and develop and pilot test an overdose risk assessment, counseling and naloxone prescription intervention for delivery in primary care settings. This study will develop a feasible, information-technology supported overdose prevention intervention for use in large health care systems. We will obtain key preliminary data to support a future large scale, multi-site randomized controlled trial of this intervention from patients and providers in three distinct health systems: an academic medical center, a managed care organization, and a safety net hospital system. The intervention will be targeted to medical clinicians who care for high-risk chronic prescription opioid users in primary care, including general medical and HIV clinics. Our Specific Aims are to: (1) Assess the knowledge, attitudes and beliefs about overdose prevention and naloxone prescription among patients, clinicians, pharmacists and clinical administrators in three health care systems. Through interviews and focus groups, we will determine the barriers and facilitators to overdose risk assessment, counseling and naloxone prescription for take-home use. (2) Develop an efficient overdose risk assessment, counseling and naloxone prescription intervention for delivery in diverse primary care practices. (3) Pilot test a randomized controlled trial of a naloxone prescription interventio that includes overdose risk assessment and counseling and determine its effects on the number of naloxone prescriptions delivered to patients This mixed methods study is responsive to federal calls for studies on widening access to naloxone and NIDA's interest in interventions to prevent drug-related injuries. Together, these aims will lead to the development of a novel intervention which has the potential to reduce fatalities from pharmaceutical opioid overdoses.